Abstract: Prostate cancer is the most frequent type of cancer and second cause of cancer-related death in men aged 65 and older. Compared to best palliative care, newly developed chemotherapy drugs and regimens increased survival, response rate, and palliation in prostate cancer patients who reached the hormone refractory stage of the disease. Therapeutical benefits from chemotherapy, however, are accompanied by adverse events shown to result in functional limitations and disability in older cancer patients. Additionally, aging-related pathophysiological vulnerability and potential social vulnerability make older hormone-refractory prostate cancer (HRPC) patients compromised hosts and place them at increased risk for negative functional status outcomes during chemotherapy. Given the impact of disability on treatment compliance, institutionalization, and death, effective interventions are needed to amend the development of disability during chemotherapy in this sizeable and compromised patient group. To develop such interventions, knowledge gaps in patterns of and risk factors for disability development during chemotherapy need to be empirically addressed. This proposed study extends previous research by prospectively examining changes in functional limitations and disability, and the impact of a series of biologic and social risk factors on disability development during chemotherapy in older HRPC patients. The specific aims of this proposed study are: (1) to describe changes in functional limitations and disability, and the longitudinal relationship between functional limitations and disability in older HRPC patients during the first 6 cycles of chemotherapy;and (2) to test the influences of biologic and social risk factors on the development of disability in older HRPC patients during the first 6 cycles of chemotherapy. It is hypothesized that levels of functional limitations and disability will increase during the first 6 cycles of chemotherapy compared to prior to chemotherapy initiation. It is further assumed that the rates of change for functional limitations and disability will be positively correlated. Finally, it is hypothesized that risk factors such as presence of frailty, more comorbidity, lower socioeconomic status, and inadequate social support will be associated with greater increases in disability over time. To accomplish these aims, self- reported data on functional limitations and disability will be collected prospectively prior and during the first 6 chemotherapy cycles, and self-reported and performance-based information on biologic and social risk factors will be collected before chemotherapy initiation. The proposed study will contribute to a better understanding of short-term patterns of and risk factors for disability development during chemotherapy in older HRPC patients;will lay the foundation for a future study examining long-term trajectories of disability in older HRPC patients;and is expected to inform the development of an intervention to avoid disability development in older HRPC patients receiving chemotherapy. The findings from this study may contribute to the achievement of the Healthy People 2010 goal of reducing illness, disability, and death caused by cancer. PUBLIC HEALTH RELEVANCE: A better understanding of short-term changes in functional limitations and disability, and of the impact of risk factors on disability development during chemotherapy in older hormone-refractory prostate cancer patients may be helpful in developing more effective interventions to prevent or reduce disability development, thereby improving public health. The proposed study will examine changes in functional limitations and disability, and relationships over time between biologic and social risk factors and changes in disability.